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A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.

PHASE1RECRUITING

A Study to Investigate the Biological Effects of Saruparib (AZD5305) Alone, Darolutamide Alone, and in Combination Given Prior to Radical Prostatectomy in Men with Newly Diagnosed Prostate Cancer (ASCERTAIN).

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Study details:

An Open-label, Randomised, Phase-I, Multi-Centre Study to Investigate the Biological Effects of Saruparib (AZD5305) alone, Darolutamide alone, and in Combination Given Prior to Radical Prostatectomy in Men with Newly Diagnosed Prostate Cancer (ASCERTAIN).

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

male participants >= 18 years old

participants deemed suitable for radical prostatectomy

participants with localised prostate cancer with unfavourable intermediate/high/very high risk eligible for prostatectomy

adequate organ and marrow function as per protocol

capable of giving signed informed consent

For participants participating in the Optional Genetic Research Only: Provision of signed and dated written Optional Genetic Research Information

Available FFPE diagnostic tumour biopsy samples

Participants must use a condom (with spermicide) from screening to 6 months after screening and refrain from fathering a child or donating sperm

Exclusion criteria

As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including HepB, hepatitis C and HIV. Screening for chronic conditions is not required.

Active HBV is defined by a known positive HBsAg result. Participants with a past or resolved HBV infection (defined as the presence of HepB antibody and absence of HBsAg) are eligible.

Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.

Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).

Participants with history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no Clinical MDS/AML suspicion, no specific screening for MDS/AML (by bone marrow/bone biopsy) is required.

Prior malignancy within 3 years of screening whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.

Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of TdP.

Any of the following cardiac criteria:

Mean resting corrected QT interval (QTcF) > 450 milliseconds or QTcF < 340 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes.

Any factors that increase the risk of QT prolongation, shortening or risk of arrhythmic events such as hypokalaemia, congenital long or short QT syndrome, family history of long QT syndrome, familial short QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong or shorten the QT interval.

Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, second or third degree atrioventricular block and clinically significant sinus node dysfunction not treated with pacemaker.

Other CVS diseases as defined by any of the following:

Symptomatic heart failure (as defined by NYHA class ≥ 2).

uncontrolled hypertension.

hypertensive heart disease with significant left ventricular hypertrophy.

History of acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to screening.

cardiomyopathy of any aetiology.

presence of clinically significant valvular heart disease.

history of atrial or ventricular arrhythmia requiring acute treatment; participants with atrial fibrillation and optimally controlled ventricular rate (heart rate < 100 bpm) are permitted.

transient ischaemic attack, or stroke within 6 months prior to screening.

participants with symptomatic hypotension at screening.

Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Saruparib (AZD5305).

History of prior malignancy, treated with chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, or other anticancer agent within 3 years of screening. Previously localised surgically treated malignancy is acceptable, if no evidence of recurrence.

Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

Prior treatment with any systemic or localised anti-cancer treatment for the localised prostate cancer.

During the 4 weeks prior to the first dose, receiving immune modulatory agents including but not limited to, continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent.

Concomitant use of medications or herbal supplements known to be:

Strong CYP3A4 inducers/inhibitors (applies for Saruparib (AZD5305) and Saruparib (AZD5305) + darolutamide arms)

Strong or moderate CYP3A4 and P-glycoprotein inducers (applies to darolutamide arm and Saruparib (AZD5305) + darolutamide arm) This is including, but not limited to, the prohibited medications listed in CSP Appendix G, or inability to stop the use thereof, at least 21 days or at least 5 half-lives (whichever is longer) before the first dose of study treatment until 30 days after the last dose of study treatment.

Treatment with any investigational agents or study interventions from a previous clinical study within 5 half-lives or 3 weeks (whichever is longer) of the first dose of study treatment.

Participants with contraindication to darolutamide for treatment arms

Unable to comply with the visits and assessments.

In the opinion of the Investigators should not be included in this study.

No treatment arm only: if any participant meets exclusion 4, 9 or 11, they are not to be included in the study.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2023-09-21

Primary completion: 2025-11-14

Study completion finish: 2025-11-14

Study type

BASIC_SCIENCE

Phase

PHASE1

Trial ID

NCT05938270

Intervention or treatment

DRUG: Saruparib (AZD5305)

DRUG: Darolutamide

OTHER: No Treatment

Conditions

• Prostate Cancer

Condition: Prostate Cancer
DRUG: Saruparib (AZD5305) and other drugs
South Brisbane, Not Specified, Australia
Sponsor: AstraZeneca

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Find a site

Closest Location:

Research Site

Research sites nearby

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Research Site
South Brisbane, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
OTHER: Saruparib (AZD5305) only Participant will receive Saruparib (AZD5305) once daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days)	DRUG: Saruparib (AZD5305) Saruparib (AZD5305) given orally once daily
OTHER: Saruparib (AZD5305) + Darolutamide Participant will receive Saruparib (AZD5305) once daily + darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).	DRUG: Saruparib (AZD5305) Saruparib (AZD5305) given orally once daily
OTHER: No Treatment No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice	OTHER: No Treatment No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice
OTHER: Darolutamide Only Participant will receive darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).	DRUG: Darolutamide Darolutamide tablet is 300mg, given BD orally, twice daily- total dose 1200mg

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Fold change in % γH2AX positive cells from baseline value in tumour samples	To assess the effects of study treatment on γH2AX change in participants with localised prostate cancer	Tumour biopsy taken at diagnosis within approx 2 months of Day 1 planned start of study treatment; post treatment tumour biopsy taken following 21 days (+ up to 7 days) of study treatment

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Severity of Treatment-Emergent AEs/SAEs per CTCAE v5.0	To assess the safety and tolerability of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Incidence of Treatment-Emergent AEs/SAEs per CTCAE v5.0	To assess the safety and tolerability of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Number of patients with abnormal laboratory values	To assess the safety and tolerability of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Change from baseline in blood pressure reported as clinically significant	To assess the safety of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Change from baseline in heart rate reported as clinically significant	To assess the safety of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Change from baseline in QTc value	To assess the safety of study treatment in participants with localised prostate cancer	Day 1 to 28 days post-surgery
Number of participants undergoing planned surgery	To assess the impact of study treatment on surgical feasibility in participants with localised prostate cancer	Measured based on Day 1 to Day 21 of treatment
Reasons of participants requiring treatment-related and non-treatment related delays of surgery and delays > 7 days from scheduled day	To assess the impact of study treatment on surgical feasibility in participants with localised prostate cancer	Measured based on Day 1 to Day 21 of treatment
Number of participants requiring treatment-related and non-treatment related delays of surgery and delays > 7 days from scheduled day	To assess the impact of study treatment on surgical feasibility in participants with localised prostate cancer	Measured based on Day 1 to Day 21 of treatment
Change in Ki-67 % positive cells from baseline in tumour samples	To assess the effects of study treatment on Ki-67 change in participants with localised prostate cancer	Measured based on Day 1 to Day 21 of treatment

Frequently Asked Questions

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References

Clinical Trials Gov: A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.